Twinstar is required for muscle development. Shannon F. Yu^1,2, Mary K. Baylies². 1) Gerstner Sloan-Kettering Graduate School, New York, NY; 2) Sloan-Kettering Institute, New York, NY.

   A conserved feature of skeletal muscle development is the formation of muscles of various shapes and sizes. These differences are intimately linked to their function; yet little is known about how a muscle achieves its distinct morphology. Drosophila provides an excellent model system to study this process: the muscle pattern, while relatively simple, consists of a repetitive arrangement of 30 discrete muscles, each defined by their shape and size. The requirement for the actin cytoskeleton and its modifiers, including Arp2/3, WASp and SCAR, has been demonstrated during embryonic, larval and adult muscle development. To date, however, only activators of actin polymerization have been shown to be necessary for proper muscle development in Drosophila. Twinstar (Cofilin) is a conserved member of a family of actin-binding proteins that disassemble actin filaments. We show that twinstar is expressed in the embryonic muscle and that loss of twinstar results in muscle loss as well as aberrant muscle-tendon attachment and sarcomere formation. Further, muscle-specific depletion of twinstar leads to embryonic lethality, due to aberrant sarcomere formation. Additionally, overexpression of wild-type and constitutively active twinstar in muscle phenocopies loss of twinstar in the embryo suggesting that Twinstar activity must be tightly regulated during muscle development. Assessment of muscle function when twinstar is overexpressed later in development indicates defects in flying, further implicating Twinstar in muscle function. Taken together, these data indicate twinstar plays multiple roles during myogenesis and suggest a critical role for actin disassembly during muscle morphogenesis.